Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death

Published on Apr 1, 2015in Food and Chemical Toxicology4.679
· DOI :10.1016/J.FCT.2015.01.017
Anna Maria Posadino19
Estimated H-index: 19
(University of Sassari),
A Cossu14
Estimated H-index: 14
(University of Sassari)
+ 7 AuthorsGianfranco Pintus32
Estimated H-index: 32
(University of Sassari)
Sources
Abstract
Abstract Studies analyzing the impact of natural antioxidants (NA) on Endothelial Cells (ECs) have dramatically increased during the last years, since a deregulated ECs redox state is at the base of the onset and progression of several cardiovascular diseases. However, whether NA can provide cardiovascular benefits is still a controversial area of debate. Resveratrol (RES), a natural polyphenol found in grapes, is believed to provide cardiovascular benefits by virtue of its antioxidant effect on the endothelium. Here, we report that tissue-attainable doses of resveratrol increased the intracellular oxidative state, thus affecting mitochondrial membrane depolarization and inducing EC death. Cyclosporine A, a mitochondrial permeability transition pore inhibitor, prevented oxidative-mediated cell death, thus implicating mitochondria in resveratrol-induced EC impairment. The specific cytochrome P450 (CYP) 2C9 inhibitor, sulfaphenazole, counteracted both oxidative stress and mitochondrial membrane depolarization, providing EC protection against resveratrol-elicited pro-oxidant effects. Our findings strongly suggest that CYP2C9 mediates resveratrol-induced oxidative stress leading to mitochondria impairment and EC death.
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